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Roula BOU KHALIL Endocrinology Division SGHUMC Assistant Professor, Balamand University Pheocromocytoma: An Update in Genetic Profiling, Diagnosis, Treatment

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OUTLINE Overview Epidemiology Updates in Genetics Diagnosis (biochemical and imaging) Treatment

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OVERVIEW

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Pheochromocytoma is a tumor arising from adrenomedullary chromaffin cells that commonly produces one or more catecholamines: epinephrine, norepinephrine, and dopamine Rarely, these tumors are biochemically silent. Paraganglioma is a tumor derived from extra-adrenal chromaffin cells sympathetic paravertebral ganglia of thorax, abdomen, and pelvis parasympathetic ganglia located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull, these do not produce catecholamines

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80 to 85% of chromaffin-cell tumors are pheochromocytomas, 15 to20%are paragangliomas During the last few years, a considerable amount of new data concerning the genetics of PHEO/PGL or PPGL 25% of cases develop secondary to germline mutations Tip of an iceberg because beyond a single tumor there is potentially a broader clinical picture

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EPIDEMIOLOGY

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Prevalence of PPGL is not precisely known Annual incidence of pheochromocytoma is approximately 0.8 per 100,000 person years Prevalence of PPGL in patients with hypertension in general outpatient clinics varies between 0.2 and 0.6% Autopsy studies demonstrate undiagnosed tumors in 0.050.1% In children with hypertension, prevalence of PPGL is approximately 1.7% Nearly 5% of patients with incidentally discovered adrenal masses on anatomical imaging prove to have a pheochromocytoma

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Equally in men and women Mean age at diagnosis 4 th 5 th decades large number of patients have non classic symptoms such as abdominal pain, vomiting, dyspnea, heart failure, hypotension, or sudden death, suggesting that the majority of PHEOs are not diagnosed during life Most PHEOs are sporadic with prevalence of malignancy 9% About 10% of patients with PHEOs present with metastatic disease at the time of their initial work-up

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At least one-third of all patients with PPGLs have disease- causing germline mutations (inherited mutations present in all cells of the body) The prevalence of PPGL in individuals carrying a germline mutation in PPGL susceptibility genes may be around 50%. Patients with hereditary PPGLs typically present with multifocal disease and at a younger age than those with sporadic neoplasms

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CLINICAL IMPORTANCE OF DIAGNOSIS Cardiovascular morbidity and mortality due to excess catecholamines if left untreated PPGL may enlarge mass effect For familial disease, detection of a tumor in the proband may result in earlier diagnosis and treatment in other family members Some PPGLs have malignant potential, defined as the presence of metastases in nonchromaffin tissue Mutations in the gene encoding SDH subunit B (SDHB) can lead to metastatic disease in 40% or more

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When to suspect pheochromocytoma? Hyperadrenergic spells Resistant hypertension A familial syndrome that predisposes to catecholamine-secreting tumors (eg, MEN2, NF1, VHL) A family history of PPGL An incidentally discovered adrenal mass Hypertension and new onset or atypical diabetes mellitus Pressor response during anesthesia, surgery, or angiography Onset of hypertension at a young age (eg,

Laparoscopic adrenalectomy Open adrenalectomy (large tumors > 8 cm, malignant disease) Partial adrenalectomy with cortical sparing in familial pheochromocytoma (High incidence of bilateral disease) to prevent permanent glucocorticoid deficiency.

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Major potential postoperative complications are hypertension, hypotension, and rebound hypoglycemia Blood pressure, heart rate and plasma glucose levels should be closely monitored for 2448 hours Measure plasma or urine levels of metanephrines on follow- up to diagnose persistent disease (2-4 weeks after surgery) Lifelong annual biochemical testing to assess for recurrent or metastatic disease

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